A stable supply of various types of blood cells in necessary amounts is extremely important for the treatment of blood-related diseases. To date, various types of blood cells have been mainly produced from blood collected from donors, and the thus produced blood cells have been used for treatments such as surgery. However, due to the chronic shortage of donors, it has not been easy to promptly secure sufficient amounts of blood cells when needed. In particular, platelets that are cells essential for blood coagulation (hemostasis) are essential for leukemia, bone marrow transplantation, anticancer therapy and like. However, since platelets collected from donors cannot be preserved in a frozen state, there is a high need for an effective means for stably supplying such platelets.
Recently, attempts have been vigorously made to produce various types of blood cells from pluripotent stem cells such as ES cells or iPS cells in vitro, without depending on the blood donation, and the practical use thereof has gained attention. For example, Takayama et al. have reported that they have succeeded in generation of platelets from human ES cells (Patent Literature 1 and Non Patent Literature 1). In addition, it has been disclosed that platelets can be produced also from iPS cells (Patent Literature 2).
As a result of the development of a method for producing blood cells from pluripotent stem cells in vitro, a majority of various types of blood cells, which will be used in medical sites in the future, would be produced from pluripotent stem cells. Thus, it is anticipated that the chronic shortage of blood cells could be overcome. However, the current situation is that only small amounts of blood cells can be produced by the previously reported methods for producing blood cells from iPS cells or ES cells, it is difficult to secure blood cells in amounts necessary for treatments such as surgery. Accordingly, in order to promote the differentiation of iPS cells or ES cells into blood cells by a certain method, it is necessary to improve conventional methods.
When cell differentiation is induced, an oxygen concentration is different between in vivo induction and in vitro induction. Several reports showed that progenitor cells were cultured in an oxygen concentration lower than an atmospheric oxygen environment and differentiated into various kinds of cells in vitro. (Non Patent Literature 2 to Non Patent Literature 5, and Patent Literature 3 to Patent Literature 5). For example, the following methods have been reported so far: a method of culturing cells capable of differentiating into cartilage under low oxygen conditions, so as to carry out cartilage differentiation (Patent Literature 3); a method of culturing undifferentiated central nervous system cells (Patent Literature 4) or neural crest stem cells (Patent Literature 5) under low oxygen conditions; a method of culturing ES cells in a low oxygen concentration and then culturing them in an atmospheric oxygen concentration, so as to differentiate the cells into cardiac muscle cells (Non Patent Literature 5); and the like. However, there have not yet been detailed reports regarding the influence of a low oxygen concentration on the differentiation of cells into blood cells.